Crystal structure of the prion protein regulatory domain in complex with the Alzheimer's peptide

Abstract

The endogenous prion protein (PrP) has been shown to play a key role in both Alzheimer's disease (AD) and prion diseases. On a fundamental level, these two neurodegenerative disorders share a common cause, the misfolding of a protein or peptide and its subsequent aggregation. In prion diseases, the healthy, properly folded cellular PrP (PrPC) can be converted into the toxic conformation, scrapie PrP (PrPSc), via a poorly understood mechanism. Aggregation of PrPSc leads to cell death. AD is most commonly associated with a peptide called amyloid beta 1-42 (Aβ(1-42)) that aggregates extracellularly and eventually forms amyloid plaques, causing neuronal degeneration in concert with intracellular neurofibrillary tangles.